A Malaria Vaccine Adjuvant Based on Recombinant Antigen Binding to Liposomes

Pfs25 is a malaria transmission-blocking vaccine antigen candidate, but its apparently limited immunogenicity in humans has hindered clinical development. Here, we show that recombinant, his-tagged Pfs25 can be mixed at the time of immunization with pre-formed liposomes containing cobalt-porphyrin-phospholipid (CoPoP), resulting in spontaneous nanoliposome antigen particleization (SNAP). Antigens are stably presented in uniformly-oriented display via his-tag insertion in the CoPoP bilayer, without covalent modification or disruption of antigen conformation. SNAP immunization of mice and rabbits is well tolerated with minimal local reactogenicity and results in orders-of-magnitude higher functional antibody generation compared to other “mix-and-inject” adjuvants. Serum-stable antigen-binding during transit to draining lymph nodes leads to enhanced antigen uptake by phagocytic antigen presenting cells, with subsequent generation of long-lived, antigen-specific plasma cells. Seamless multiplexing with four additional his-tagged Plasmodium falciparum polypeptides induces strong and balanced antibody production, illustrating the simplicity of developing multi-stage particulate vaccines with SNAP immunization.